H. pylori activates NF-κB through a signaling pathway involving IκB kinases, NF-κB—inducing kinase, TRAF2, and TRAF6 in gastric cancer cells

Maeda, Shin; Yoshida, Haruhiko; Ogura, Keiji; Mitsuno, Yuzo; Hirata, Yoshihiro; Yamaji, Yutaka; Akanuma, Masao; Shiratori, Yasushi; Omata, Masao

doi:10.1053/gast.2000.8540

Cited by 184 publications

(158 citation statements)

References 67 publications

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“…The role of TRAF6 has primarily been studied in innate immunity in response to harmful stimuli (40,41). TRAF6 has also been intermittently investigated in several cancer cells (38,39,42,43). Activation of some signaling mechanisms, including Akt pathway, have been suggested to be involved in TRAF6-mediated oncogenesis (39).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-146a Downregulates NFκB Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma

Paik

Jang

Jeon³

et al. 2011

Clinical Cancer Research

164

152

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Purpose: We investigated prognostic implications of microRNAs in extranodal NK/T cell lymphoma (NKTL). Experimental Design: We measured miRNA expression in NKTL tissues and cell lines, using real-time PCR, and analyzed its role in NKTL, using cell lines. Results: Multivariate analysis showed low miR-146a expression (P < 0.001; HR = 13.110), primary non–upper aerodigestive tract lesion (non-UAT; P = 0.008; HR = 5.376) and high International Prognostic Index (IPI; ≥3; P = 0.013; HR = 3.584) to be independent poor prognostic factors. miR-146a expression could subdivide UAT-NKTL into 2 prognostic groups, resulting in the following prognostic groups: (i) UATLow-146a, (ii) UATHigh-146a, and (iii) non-UAT. Compared with UATHigh-146a, UATLow-146a showed distinctively poor prognosis (P < 0.001; HR = 15.620), similar to the non-UAT group. In vitro, miR-146a overexpression in NKTL cell lines, SNK6 and YT, inhibited nuclear factor κB (NFκB) activity, suppressed cell proliferation, induced apoptosis, and enhanced chemosensitivity. TNF receptor–associated factor 6, a target of miR-146a and a known NFκB activator, was downregulated by miR-146a in SNK6 and YT cells. Promoter methylation of miR-146a gene was observed in SNK6 and YT cells, as well as in NKTL tissues with low miR-146a expression, and miR-146a expression was induced by the conversion of methylation status with a demethylating agent in SNK6 and YT cells. Conclusions: These results suggest that miR-146a might function as a potent tumor suppressor in NKTL and be useful for patient assessment and therapeutic targeting. Clin Cancer Res; 17(14); 4761–71. ©2011 AACR.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-146a Downregulates NFκB Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma

Paik

Jang

Jeon³

et al. 2011

Clinical Cancer Research

164

152

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“…The choice of the bacterial strain was based on the prevalent role of the cag pathogenicity island in gastric diseases and induction of initial events necessary for interaction with epithelial cells (40) and subsequent gene activation (41). Although not a strict equivalent to gastric cell lines, Hep-2, HT-29, T-84, Madin-Darby canine kidney cells, or Caco-2 cells have been used consistently to study IL-8 release, H. pylori-host interaction, permeability increase, and polymorpho-nuclear leukocyte migration (42)(43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Microaerophilic Conditions Permit to Mimic in VitroEvents Occurring during in Vivo Helicobacter pylori Infection and to Identify Rho/Ras-associated Proteins in Cellular Signaling

Cottet

Corthésy–Theulaz

Spertini

et al. 2002

Journal of Biological Chemistry

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Molecular dissection of the mechanisms underlyingHelicobacter pylori infection suffers from the lack of in vitro systems mimicking in vivo observations. A system was developed whereby human epithelial cells (Caco-2) grown as polarized monolayers and bacteria can communicate with each other under culture conditions optimal for each partner. Caco-2 cells grown on filter supports were inserted in a vertical position into diffusion chambers equilibrated with air and 5% CO 2 at their basolateral surface (aerophilic conditions) and 5% CO 2 , 5% O 2 , 90% N 2 (microaerophilic conditions) in the apical compartment. Remarkably, the epithelial polarized layer was stable under these asymmetric culture conditions for at least 24 h, and the presence of Caco-2 cells was necessary to maintain H. pylori growth. In contrast to previous studies conducted with non-polarized Caco-2 cells and other cell lines kept under aerophilic conditions, we found H. pylori-dependent stimulation of cytokine secretion (MCP-1 (monocyte chemoattractant protein-1), GRO-␣ (growth-regulated oncogene-␣), RANTES (regulated on activation normal T cell expressed and secreted)). This correlated with nuclear translocation of NF-B p50 and p65 subunits. Tyrosine phosphorylation of nine cellular proteins was induced or enhanced; we identified p120RasGAP , p190 RhoGAP , p62dok (downstream of tyrosine kinases), and cortactin as H. pylori-inducible targets. Moreover, reduction of H. pylori urease expression was observed in adherent bacteria as compared with bacteria in suspension. In addition to mimicking several observations seen in the inflamed gastric mucosa, the novel in vitro system was allowed to underscore complex cellular events not seen in classical in vitro analyses of microaerophilic bacteria-epithelial cell cross-talk.

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“…23 The authors suggested that H3Ser10 phosphorylation increased the ability of the transcription factor NFκB to access chromatin. Since H. pylori is a potent inducer of NFκB, 24 we wanted to know whether H. pylori-mediated NFκB activation is linked with the observed histone phosphorylation changes. Therefore, we silenced the NFκB activation pathway employed by H. pylori: 25 the two catalytic subunits of the IKK complex, IKKα and IKKβ, were silenced using RNA interference.…”

Section: H Pylorimentioning

confidence: 99%

Helicobacterpylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation

Fehri¹,

Rechner²,

Janßen³

et al. 2009

Epigenetics

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H. pylori activates NF-κB through a signaling pathway involving IκB kinases, NF-κB—inducing kinase, TRAF2, and TRAF6 in gastric cancer cells

Cited by 184 publications

References 67 publications

MicroRNA-146a Downregulates NFκB Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma

MicroRNA-146a Downregulates NFκB Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma

Microaerophilic Conditions Permit to Mimic in VitroEvents Occurring during in Vivo Helicobacter pylori Infection and to Identify Rho/Ras-associated Proteins in Cellular Signaling

Helicobacterpylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation

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